Budesonide is a synthetic steroid of the glucocorticoid family with a high topical anti-inflammatory activity. Enteric-coated formulations resist gastric-acid degradation, delivering active drug to the small intestine and proximal colon. Budesonide has a high first-pass metabolism with minimal systemic absorption. It is therefore felt to cause fewer side effects than traditional glucocorticosteroids and to be generally well tolerated. The aim of this paper is to examine the utility of this medication in frequently encountered gastrointestinal conditions: Crohn's disease, ulcerative colitis, microscopic colitis and eosinophilic oesophagitis. A Medline search was performed to find published original research and review articles relating to the use budesonide in common gastroenterological conditions. The results showed that budesonide is efficacious in the induction and short-term maintenance of Crohn's disease. Budesonide is the best-documented treatment for microscopic colitis. It is well proven to be effective in the induction of remission in collagenous colitis but its use in lymphocytic colitis remains less well documented. In conclusion, budesonide is an effective glucocorticosteroid therapy for many chronic gastrointestinal diseases. In combination with its efficacy, the low incidence of serious side effects associated with this drug should keep it at the forefront in the therapeutic arsenal of any gastroenterologist.
budesonide; Crohn's disease; eosinophilic oesophagitis; microscopic colitis; pouchitis; ulcerative colitis
Budesonide, a potent glucocorticoid, is used for the treatment of inflammatory bowel diseases. Current available oral formulations of budesonide have low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. In this paper a pH- and time-controlled colon-targeted pellet-based tablet of budesonide was established. Pellet cores were prepared by extrusion-spheronization method and further coated with xanthan gum (barrier layer), Eudragit NE30D and L30D55 combination (inner layer), and Eudragit FS30 (as enteric layer) sequentially to achieve the required release profile. The coated pellets then compressed into tablets using inert tabletting granules of Cellactose or Pearlitol. Release studies, performed in simulated gastric, intestinal, and colon pH were used in sequence to mimic the gastrointestinal transit. The influence of formulation variables like barrier layer thickness, inner layer composition, and enteric coat thickness on drug release were investigated and the coated pellets that contained 12% weight gain in xanthan gum layer, Eudragit L30D55 and Eudragit NE30D with a ratio of 3 : 7 in inner layer with 30% weight gain and 25% weight gain in Eudragit FS layer were found to protect the drug release in stomach and small intestine and 83.35 ± 2.4 of budesonide was released at 24 h. The drug release from the tablets prepared using 40% Cellactose 80 as tableting excipient was found to be closely similar to that of uncompressed pellets.
Although oral glucocorticoids are the treatment of choice for moderate to severe ulcerative pancolitis, their systemic side effects and adrenal suppression account for considerable morbidity. An oral glucocorticoid-conjugate (prodrug), budesonide-beta-D-glucuronide, which is not absorbed in the small intestine but is hydrolysed by colonic bacterial and mucosal beta-glucuronidase to release free budesonide into the colon was synthesised. The objective of this study was to compare treatment with budesonide-beta-D-glucuronide with treatment with free budesonide by examining: (1) the healing of experimental colitis and (2) the extent of adrenal suppression. Pancolitis was induced with 4% acetic acid. Animals were then randomised to receive oral therapy for 72 hours with (1) budesonide-beta-D-glucuronide, (2) free budesonide, or (3) vehicle. Drug efficacy and colitic healing was determined by measuring gross colonic ulceration, myeloperoxidase activity, and in vivo colonic fluid absorption. Adrenal suppression was determined by measuring plasma adrenocorticotrophic hormone and serum corticosterone. Vehicle-treated colitis animals had gross ulceration, increased myeloperoxidase activity, and net colonic fluid secretion. Treatment with oral budesonide-beta-D-glucuronide accelerated all measures of colitis healing at a fourfold lower dose than did free budesonide. Furthermore, treatment with budesonide-beta-D-glucuronide did not result in adrenal suppression whereas free budesonide treatment did. A newly synthesised orally administered glucocorticoid-conjugate accelerates colitis healing with limited adrenal suppression. Development of an orally administered colon-specific steroid delivery system represents a novel approach to inflammatory bowel disease treatment.
Eosinophilic gastroenteritis (EGE) in the adult is a distinctive pathologically-based disorder characterized by an eosinophil-predominant mucosal inflammatory process. Most often, the disorder is detected during endoscopic investigation for abdominal pain or diarrhea. Other causes of gastric and intestinal mucosal eosinophilia require exclusion, including parasitic infections and drug-induced causes. Occasionally, the muscle wall or serosal surface may be involved. EGE appears to be more readily recognized, in large part, due to an evolution in the imaging methods used to evaluate abdominal pain and diarrhea, in particular, endoscopic imaging and mucosal biopsies. Definition of EGE, however, may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not well standardized. Also, the eosinophilic inflammatory process may be either patchy or diffuse and the detection of the eosinophilic infiltrates may vary depending on the method of biopsy fixation. Treatment has traditionally focused on resolution of symptoms, and, in some instances, eosinophil quantification in pre-treatment and post-treatment biopsies. Future evaluation and treatment of EGE may depend on precise serological biomarkers to aid in definition of the long-term natural history of the disorder and its response to pharmacological or biological forms of therapy.
Eosinophils; Eosinophilic gastroenteritis; Eosinophilic gastritis; Eosinophilic enteritis
desirable to prescribe the minimal effective dose of inhaled steroids
to control asthma. To ensure that inflammation is suppressed whilst
using the lowest possible dose, a sensitive and specific method for
assessing airway inflammation is needed.
of exhaled nitric oxide (NO), sputum eosinophils, and methacholine
airway responsiveness (PC20) for monitoring airway
inflammatory changes following four weeks of treatment with an inhaled
corticosteroid (budesonide via Turbohaler) were compared. Mild stable
steroid naive asthmatic subjects were randomised into two double blind,
placebo controlled studies. The first was a parallel group study
involving three groups receiving either 100 µg/day budesonide (n = 8), 400 µg/day budesonide (n = 7), or a matched placebo (n = 6). The
second was a crossover study involving 10 subjects randomised to
receive 1600 µg budesonide or placebo. The groups were matched with
respect to age, PC20, baseline FEV1 (% predicted), exhaled NO, and sputum eosinophilia.
significant improvements in FEV1 following 400 µg and
1600 µg budesonide (11.3% and 6.5%, respectively, p<0.05). This
was accompanied by significant reductions in eosinophil numbers in
induced sputum (0.7 and 0.9 fold, p<0.05). However, levels of exhaled
NO were reduced following each budesonide dose while PC20
was improved only with 1600 µg budesonide. These results suggest
that exhaled NO and PC20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in
sputum. There were dose dependent changes in exhaled NO, sputum eosinophils, and PC20 to inhaled budesonide but a plateau
response of exhaled NO was found at a dose of 400 µg daily.
the number of eosinophils in induced sputum may be the most accurate
guide to establish the minimum dose of inhaled steroids needed to
control inflammation. This, however, requires further studies involving
a larger number of patients.
Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor.
The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7–10 days, with each episode lasting for 1–3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed.
The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF) and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.
Eosinophilic gastroenteritis (EGE) is an eosinophil-predominant inflammatory process that may be detected in endoscopic gastric or intestinal biopsies. The long-term natural history and effects of EGE treatment are not known. A 44-year-old man with abdominal pain was treated with oral ketotifen and followed for more than 20 years. Ketotifen provided symptomatic benefit, with prompt clinical relapse if the drug was discontinued. However, despite the use of ketotifen, the endoscopic abnormalities persisted and appeared to progress. Gastric body and antral mucosal folds appeared thickened, erythematous and friable, with minimal erosive change. Later, even during long asymptomatic periods suggesting clinical ‘remission’, inflammatory polypoid change, previously described in children with EGE, developed with mucosal ‘pock-marking’ and apparent scarring. Ketotifen treatment does not appear to prohibit or reverse the inflammatory process in the gastric mucosa in EGE, although long-term effects of steroids may be avoided. In the future, treatment of EGE may involve monoclonal antibody agents that target the specific biological effects of the eosino-phil, apparently central to this unusual inflammatory process.
Eosinophilic gastroenteritis; Eosinophils; Gastric polyps; Ketotifen; Mast cells
Eosinophilic gastroenteritis (EG) is characterized by eosinophilic infiltration of the bowel wall and variable gastrointestinal manifestations. Clinicians should have a high index of suspicion for EG when faced with gastrointestinal symptoms and peripheral eosinophilia to avoid incorrect diagnosis and inappropriate treatments. A 24-year-old woman was admitted to our hospital complaining of acute right lower quadrant abdominal pain and a laparoscopic appendectomy performed for a presumed diagnosis of an acute appendicitis. However, the procedure revealed bowel edema and a moderate amount of ascites without evidence of a suppurative appendicitis. Postoperatively, she showed persistent and progressive eosinophilia, exudative eosinophilic ascites, eosinophilic infiltration of the resected appendix wall, and eosinophilic infiltration of gastroduodenal mucosa. A punch biopsy of the abdominal skin also revealed inflammation with marked eosinophilic infiltration of the skin. She recovered after the treatment with a low dose of steroid for the EG with eosinophilic dermatitis. EG with eosinophilic dermatitis has not been reported yet and is considered fortuitous in this case.
Eosinophil; gastroenteritis; dermatitis; ascites; corticosteroids
Eosinophilic gastroenteritis (EG) is an uncommon disorder, characterised by cramping abdominal pain, diarrhoea and vomiting and histologically by eosinophilic infiltration of bowel wall. We present a patient who developed EG during the course of a systemic, necrotising vasculitis, who became critically ill after failure of treatment with corticosteroids and cytotoxic drugs and responded only to oral sodium chromoglycate.
Eosinophilic gastroenteritis is defined as a disorder that selectively affects the gastrointestinal tract with eosinophil-rich inflammation in the absence of any known causes for eosinophilia. The clinical manifestations vary according to the site of the eosinophilic infiltrated layer of the bowel wall. Eosinophilic enteritis presenting as intussusception in adult has not been previously reported in the literature. Especially, making the diagnosis of intussusception in adults is often difficult due to the variable clinical findings. In our case, the correct diagnosis of intussusception due to eosinophilic enteritis was arrived at rather easily based on the ultrasonography and endoscopic biopsy. The patient was treated with oral prednisolone at 30 mg/day for 7 days, and then the drug was tapered off for 2 months; we didn't perform surgery. He has been asymptomatic for about 1 year after discharge without disease recurrence.
Eosinophils; Enteritis; Intussusception; Steroids
We report a seven year history of a 23 year old woman born in the Antilles, with pseudotumoral enterocolitis and massive eosinophilia. In 1973 she developed a haemorrhagic colitis with massive peripheral eosinophilia of up to 60000/mm3. Medical treatment, mainly corticosteroids, failed to control the disease. The patient temporarily improved after colectomy and remained in remission for two years. In 1978 the disease recurred in the rectum and small intestine with formation of tumour-like granulomata and massive infiltration by eosinophils, unresponsive to corticosteroids. Intestinal blood and protein loss continued until death seven years after onset. In spite of exhaustive investigation, no parasites, allergens, or other aetiological agents could be found. As only the gut was infiltrated, the hypereosinophilic syndrome could be excluded. The enterocolitis here described does not correspond to an eosinophilic gastroenteritis, nor to other known inflammatory bowel diseases and to our knowledge has not been reported previously.
Budesonide/formoterol is an effective treatment for both asthma and chronic obstructive pulmonary disease. This study compared the efficacy and safety of a novel hydrofluoroalkane (HFA) pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol with that of budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI; Turbuhaler®).
This was a 12-week, multinational, randomised, double-blind, double-dummy study involving patients aged ≥ 12 years with asthma. All patients had a forced expiratory volume in 1 s of 50–90% predicted normal and were inadequately controlled on inhaled corticosteroids (500–1600 mu g/day) alone. Following a 2-week run-in, during which they received their usual medication, patients were randomised (two inhalations twice daily) to budesonide pMDI 200 mu g, budesonide/formoterol DPI 160/4.5 mu g or budesonide/formoterol pMDI 160/4.5 mu g. The primary efficacy end-point was change from baseline in morning peak expiratory flow (PEF).
In total, 680 patients were randomised, of whom 668 were included in the primary analysis. Therapeutically equivalent increases in morning PEF were observed with budesonide/formoterol pMDI (29.3 l/min) and budesonide/formoterol DPI (32.0 l/min) (95% confidence interval: −10.4 to 4.9; p = 0.48). The increase in morning PEF with budesonide/formoterol pMDI was significantly higher than with budesonide pMDI (+28.7 l/min; p < 0.001). Similar improvements with budesonide/formoterol pMDI vs. budesonide pMDI were seen for all secondary efficacy end-points. Both combination treatments were similarly well tolerated.
Budesonide/formoterol, administered via the HFA pMDI or DPI, is an effective and well-tolerated treatment for adult and adolescent patients with asthma, with both devices being therapeutically equivalent.
Gastrointestinal involvement is frequent in patients with systemic lupus erythematosus (SLE). Eosinophilic gastroenteritis, however, has only rarely been described in rheumatological conditions, despite its reported connection to autoimmune diseases, such as hypereosinophilic syndrome, vasculitides, and systemic mastoidosis. It presents typically with abdominal pain and diarrhea and is only exceptionally associated with ascites. Diagnosis can be problematic, as several other clinical conditions (malignancies, infection/tuberculosis, and inflammatory bowel diseases) have to be ruled out. It is basically a nonsurgical disease, with excellent recovery on conservative treatment. We report the rare case of a young woman with overlap syndrome who presented with abdominal pain and ascites. The diagnosis of eosinophilic enteritis was made based on clinical, radiological, and laboratory criteria. The patient was treated with corticosteroids with excellent response.
Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.
Esophageal remodeling occurs in eosinophilic esophagitis (EE) patients but whether the components of remodeling in the subepithelium are reversible by administration of topical oral corticosteroids is unknown.
We quantitated the degree of lamina propria remodeling in esophageal biopsies obtained before and after at least 3 months of therapy with budesonide in 16 pediatric EE subjects. In addition, we investigated whether corticosteroid therapy modulated vascular activation (expression of VCAM-1; level of interstitial edema), TGFβ1 activation (levels of TGFβ1, phosphorylated Smad2/3), and performed a pilot analysis of a polymorphism in the TGFβ1 promoter in relation to EE subjects who had reduced remodeling with budesonide therapy.
EE subjects were stratified based on the presence (n = 9) or absence (n = 7) of decreased epithelial eosinophilia following budesonide. Patients with residual eosinophil counts of ≤ 7 eosinophils per high power field in the epithelial space (responders) demonstrated significantly reduced esophageal remodeling with decreased fibrosis, TGFβ1 and pSmad2/3 positive cells, and decreased vascular activation in association with budesonide therapy. Responders were more likely to have a CC genotype at the −509 position in the TGFβ1 promoter.
Reductions in epithelial eosinophils following budesonide therapy were associated with significantly reduced esophageal remodeling.
budesonide; eosinophilic esophagitis; pediatric; remodeling; transforming growth factor-beta (TGFβ)
Background: Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established.
Aims: To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis.
Patients: Twenty patients with collagenous colitis (collagen layer >10 μm) and diarrhoea (>4 stools/day and/or stool weight >200 g/day).
Methods: A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis.
Results: Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment.
Conclusions: Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.
collagenous colitis; microscopic colitis; diarrhoea; inflammatory bowel disease; morphometry; randomised controlled trial
This retrospective, observational cohort study aimed to compare treatment outcomes and healthcare costs in the year after initiation of maintenance treatment with budesonide/formoterol or salmeterol/fluticasone in a German healthcare setting.
Data on German asthma patients initiating treatment with budesonide/formoterol or salmeterol/fluticasone between June 2001 and June 2005 were obtained from the IMS Disease Analyzer database. The primary outcome was the probability of treatment success, defined according to short-acting β2-agonist prescriptions and switches or addition of controller medications, during the postindex year. A secondary definition of treatment success included hospitalisations and oral corticosteroid (OCS) prescriptions. Secondary outcomes included severe asthma exacerbations, defined as ≥1 OCS prescription, asthma-related hospitalisation and/or referral. The effect of treatment on costs was estimated using generalised linear models, adjusting for patient and physician characteristics.
There were no significant differences between the budesonide/formoterol (n=1456) and salmeterol/fluticasone (n=982) groups in disease severity markers in the pre-index year. Patients on budesonide/formoterol had a 44% greater probability of treatment success [odds ratio (OR): 1.44; p = 0.0003] according to the primary definition and a 26% greater probability (OR: 1.26; p = 0.0119) according to the secondary definition, fewer severe exacerbations (−33.4%; p = 0.0123) and fewer OCS prescriptions (−31.5%; p = 0.0082) compared with salmeterol/fluticasone, after controlling for baseline characteristics. Adjusting for covariates, budesonide/formoterol had a significant inverse relationship on asthma-related costs compared with salmeterol/fluticasone (−13.4%; p < 0.001). Total cost (asthma- and non-asthma-related costs) was 12.6% lower for budesonide/formoterol (p < 0.0001).
This study suggests that for patients with chronic asthma in Germany, budesonide/formoterol rather than salmeterol/fluticasone had a higher likelihood of treatment success, and that budesonide/formoterol is the less costly option. Although the cohorts appeared to be well matched at baseline, the results should be interpreted with caution given the observational nature of the study.
BACKGROUND AND AIMS: To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD). PATIENTS AND METHODS: Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment. RESULTS: Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups. CONCLUSION: 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.
A patient with a 15 year history of diarrhoea of unknown origin is described. Scintigraphy with technetium-99m labelled albumin suggested albumin loss at the terminal ileum and caecum; subsequent colonoscopic biopsies of these macroscopically normal looking areas showed abundant infiltration with eosinophils. A diagnosis of eosinophilic enterocolitis was made. Treatment with prednisolone had good results, but had to be stopped because of severe side effects. Oral cromoglycate and mesalazine were not effective. Budesonide (CIR), a new topically active corticosteroid with very little systemic effects, was at least as effective as prednisolone without producing side effects.
This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 μg/day) received budesonide/formoterol 160/4.5 μg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 μg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 μg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p = 0.0034 and p = 0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49–0.76, p < 0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57–0.90, p = 0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol.
In some patients, eosinophilic gastroenteritis(EG) occurs in those with food allergy. We experienced a non-atopic asthmatic who had an EG associated with food allergy to fish and eggs, and blood eosinophilia. A skin prick test and RAST to causative food allergens showed a negative result. A fiber-optic endoscopic biopsy from the gastric mucosa showed an intense eosinophilic infiltration. We could find symptomatic improvement and a disappearance of eosinophilic infiltration in gastric mucosa after complete avoidance from the causative food and oral cortcosteroid. It was suggested that fiber-optic endoscopic biopsy might be needed to identify coexisting EG if an allergic patient with blood eosinophilia complains of severe gastrointestinal symptoms.
Eosinophilic gastroenteritis most commonly involves the stomach and proximal small intestine with eosinophilic inflammation of either the mucosa, submucosa or serosa. The patient reported here had isolated eosinophilic colitis. The initial presentation with iron deficiency anaemia owing to occult gastrointestinal blood loss emphasises the need to evaluate the entire gastrointestinal tract in patients with eosinophilic gastroenteritis.
Screening-CT identifies small peripheral lung nodules, some of which may be pre- or early invasive neoplasia. Secondary endpoint analysis of a previous chemoprevention trial in individuals with bronchial dysplasia showed reduction in size of peripheral nodules by inhaled budesonide.
We performed a randomized, double-blind, placebo-controlled phase IIb trial of inhaled budesonide in current and former smokers with CT-detected lung nodules that were persistent for at least one year. A total of 202 individuals received inhaled budesonide 800 µg twice daily or placebo for one year. The primary endpoint was the effect of treatment on target nodule size in a per-person analysis after one year.
The per-person analysis showed no significant difference between the budesonide and placebo arms (response rate 2% and 1%, respectively). Although the per-lesion analysis revealed a significant effect of budesonide on regression of existing target nodules (p=0.02), the appearance of new lesions was similar in both groups and thus the significance was lost in the analysis of all lesions. The evaluation by nodule type revealed a non-significant trend toward regression of non-solid and partially solid lesions after budesonide treatment. Budesonide was well tolerated with no unexpected side effects identified.
Treatment with inhaled budesonide for one year did not significantly affect peripheral lung nodule size. There was a trend toward regression of non-solid and partially solid nodules after budesonide treatment. Since a subset of these nodules is more likely to represent precursors of adenocarcinoma, additional follow-up is needed. (ClinicalTrials.gov number, NCT00321893)
chemoprevention; lung cancer; helical CT; budesonide
Blockade of cytotoxic T-lymphocyte antigen-4 (CTLA-4)
by ipilimumab leads to immune-mediated tumor regression and immune-related
adverse events (irAEs), including diarrhea and colitis. The current
analyses were undertaken to promote an understanding of the underlying
mechanism of action and to identify potential biomarkers that could
help in the prediction and management of ipilimumab-induced gastrointestinal
irAEs. Treatment-naïve or previously treated patients with
unresectable stage III/IV melanoma (n = 115)
received open-label ipilimumab (10 mg/kg every
3 weeks for four doses) and were randomized to receive concomitant
blinded prophylactic oral budesonide (9 mg/d with
gradual taper through week 16) or placebo. Outcome measures included
histologic assessment of bowel biopsies and assessment of serologic
markers of inflammatory bowel disease (IBD), fecal calprotectin
levels, and polymorphisms in immune-related genes. Ipilimumab resulted
in dysregulation of gastrointestinal mucosal immunity as evidenced
by altered antibody levels to enteric flora, inflammatory cell infiltration
into gastrointestinal mucosa, and increased fecal calprotectin associated
with diarrhea and clinical evidence of colitis. The pattern of ipilimumab-induced
antibody titers to microbial flora and the histologic features and
location of the inflammation were distinct from classic IBD. Prophylactic budesonide
did not prevent ipilimumab-induced bowel inflammation. Despite an
observed association between colonic inflammation and grade 2 or
higher diarrhea, no baseline biomarkers could reliably predict development
of gastrointestinal toxicity. Although classic IBD and ipilimumab-related
gastrointestinal toxicity are both immune mediated, the observed
pattern of biomarkers suggests ipilimumab-related gastrointestinal
toxicity may be a distinct clinicopathologic entity.
human; melanoma; ipilimumab; CTLA-4; gastrointestinal; immune-related
We report a case of eosinophilic enteritis involving the proximal small bowel, a relatively rare entity, presenting unusually as enteroliths in a 68-year-old man with complaints of anemia, malena and abdominal pain. The disease if diagnosed in the initial stages responds well to medical treatment but if associated with complications or misdiagnosed, surgical modality is the treatment of choice. In our case, the patient presented with enteroliths and strictures. Resection and anastomosis of the small bowel containing stones was carried out. Histopathology confirmed the diagnosis as eosinophilic enteritis.
Eosinophilic enteritis; Enteroliths; Eosinophils; Gastroenteritis